What are the current guidelines for managing Hepatitis C (HCV)?

Current Guidelines for Hepatitis C Management

Direct-acting antiviral (DAA) therapy is the standard of care for all patients with chronic hepatitis C infection, with treatment regimens selected based on viral genotype, presence of cirrhosis, and prior treatment history. 1

Screening and Pre-Treatment Assessment

• Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment 2
• Determine HCV genotype (1-6) and viral load to guide treatment selection
• Assess liver fibrosis stage using non-invasive methods (FibroScan, APRI, FIB-4)
• Evaluate for presence of cirrhosis and its severity (compensated vs. decompensated)
• Review medication history for potential drug-drug interactions

Treatment Regimens by Patient Population

For Treatment-Naïve Patients Without Cirrhosis:

• Glecaprevir/pibrentasvir for 8 weeks (pan-genotypic) 1
• Sofosbuvir/velpatasvir for 12 weeks (pan-genotypic) 1
• Ledipasvir/sofosbuvir for 12 weeks (can shorten to 8 weeks if HCV RNA <6 million IU/mL) (genotype 1) 1
• Elbasvir/grazoprevir for 12 weeks (genotype 1,4) 1

For Treatment-Naïve Patients With Compensated Cirrhosis:

• Glecaprevir/pibrentasvir for 12 weeks (pan-genotypic) 1
• Sofosbuvir/velpatasvir for 12 weeks (pan-genotypic) 1
• Ledipasvir/sofosbuvir for 12 weeks (genotype 1,4,5,6) 1
• Elbasvir/grazoprevir for 12 weeks (genotype 1,4) 1

For Treatment-Experienced Patients:

• Sofosbuvir/velpatasvir for 12 weeks (pan-genotypic) 1
• Glecaprevir/pibrentasvir for 8-12 weeks (duration based on cirrhosis status) 1
• Ledipasvir/sofosbuvir + ribavirin for 12 weeks or ledipasvir/sofosbuvir for 24 weeks (genotype 1) 1

For Patients With Decompensated Cirrhosis:

• Sofosbuvir/velpatasvir + ribavirin for 12 weeks 2

Special Populations

HCV/HBV Co-infection

• Monitor for HBV reactivation during and after HCV treatment 2
• HBV reactivation has been reported in HCV/HBV co-infected patients undergoing DAA therapy, sometimes resulting in fulminant hepatitis, hepatic failure, and death 2, 3
• Consider initiating HBV antiviral therapy if indicated 2

Treatment Failures

• For patients who fail first-line DAA therapy, sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is recommended 4
• NS5A inhibitor resistance-associated substitutions (RASs) may persist for more than 2 years, while NS3-4A variants often disappear gradually after DAA therapy is stopped 4
• For patients who fail an NS5A inhibitor, consider deferring treatment if they don't have cirrhosis or urgent need for re-treatment 4
• If re-treatment is needed, use sofosbuvir as backbone therapy plus a drug from a class other than previously used, for 24 weeks, with weight-based ribavirin 4

Treatment Outcomes and Monitoring

• Modern DAA regimens achieve sustained virological response (SVR) rates of 95-100% across all genotypes 1
• Monitor HCV RNA at baseline, during treatment (if indicated), at end of treatment, and 12 weeks after treatment completion to determine SVR
• Most regimens are well-tolerated with minimal side effects including fatigue, headache, nausea, and nasopharyngitis 1
• Ribavirin-containing regimens may cause anemia and require monitoring of hemoglobin levels 1

Drug-Drug Interactions

• Avoid coadministration of DAAs with potent inducers like St. John's Wort or rifampin as they can significantly decrease plasma concentrations of DAAs 5
• Exercise caution when using DAAs with first-generation anticonvulsants (carbamazepine, phenytoin, phenobarbital) due to potential interactions 6
• Review all concomitant medications before initiating DAA therapy

Future Directions

• Oral drug combinations without interferon are now standard of care, offering high SVR rates with minimal side effects 7
• Combined drug regimens with different mechanisms of action are necessary to prevent the emergence of drug-resistant HCV 7
• The optimal treatment for patients with multidrug-resistant variants remains an area of ongoing research 4